Leora Horn1, Scott Gettinger2, D Ross Camidge3, Egbert F Smit4, Yelena Y Janjigian5, Vincent A Miller6, William Pao7, Matthias Freiwald8, Jean Fan9, Bushi Wang10, Vikram K Chand11, Harry J M Groen12. 1. Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu. 2. Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, FMP 127, New Haven, CT, USA. Electronic address: scott.gettinger@yale.edu. 3. University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu. 4. Vrije Universiteit VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: EF.Smit@vumc.nl. 5. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E66th Street, Room 1033, New York, NY, USA. Electronic address: janjigiy@mskcc.org. 6. Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA. Electronic address: vmiller@foundationmedicine.com. 7. Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: william.pao@vanderbilt.edu. 8. Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach, Germany. Electronic address: matthias.freiwald@boehringer-ingelheim.com. 9. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: jean.fan@boehringer-ingelheim.com. 10. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: bushi.wang@boehringer-ingelheim.com. 11. Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: vikramkchand@gmail.com. 12. University of Groningen and University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl.
Abstract
OBJECTIVES: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. MATERIALS AND METHODS: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. RESULTS: Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks was 4.9 versus 1.8 months (p=0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p=0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. CONCLUSION: Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib. CLINICALTRIALS. GOV IDENTIFIER: NCT01090011.
OBJECTIVES: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. MATERIALS AND METHODS:Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. RESULTS: Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks was 4.9 versus 1.8 months (p=0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p=0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. CONCLUSION: Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib. CLINICALTRIALS. GOV IDENTIFIER: NCT01090011.
Authors: Jonathan W Riess; David R Gandara; Garrett M Frampton; Russell Madison; Nir Peled; Jose A Bufill; Grace K Dy; Sai-Hong Ignatius Ou; Philip J Stephens; John D McPherson; Primo N Lara; Rebekah A Burich; Jeffrey S Ross; Vincent A Miller; Siraj M Ali; Philip C Mack; Alexa B Schrock Journal: J Thorac Oncol Date: 2018-07-05 Impact factor: 15.609
Authors: Zhenfang Du; Benjamin P Brown; Soyeon Kim; Donna Ferguson; Dean C Pavlick; Gowtham Jayakumaran; Ryma Benayed; Jean-Nicolas Gallant; Yun-Kai Zhang; Yingjun Yan; Monica Red-Brewer; Siraj M Ali; Alexa B Schrock; Ahmet Zehir; Marc Ladanyi; Adam W Smith; Jens Meiler; Christine M Lovly Journal: Nat Commun Date: 2021-03-02 Impact factor: 14.919
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